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人卵巢癌裸鼠异种移植瘤的过继性细胞免疫治疗

Adoptive cellular immunotherapy of human ovarian carcinoma xenografts in nude mice.

作者信息

Ortaldo J R, Porter H R, Miller P, Stevenson H C, Ozols R F, Hamilton T C

出版信息

Cancer Res. 1986 Sep;46(9):4414-9.

PMID:3089592
Abstract

Adoptive cell therapy with various purified populations of human lymphoid and monocytoid effector cells which have been in vitro activated with recombinant interleukin 2 and gamma-interferon was performed in an in vivo nude mouse model of human ovarian cancer. Administration i.p. of human interleukin 2-activated populations of large granular lymphocytes resulted in a significant extension of mean survival time (30 to 60 days) in this ovarian carcinoma model. In addition, T-cells activated with interleukin 2, in a similar fashion to large granular lymphocytes, also significantly prolonged survival of animals with ovarian carcinoma. In contrast, monocytes, with or without gamma-interferon activation, did not improve survival of tumor-bearing mice. In vitro results using direct isotopic release assays to measure efficacy of effectors against the ovarian cancer cells before and after activation, especially the activated natural killer cells, paralleled the effects on survival in the nude mouse model. However, the results with T-cells were somewhat inconsistent in vitro regarding their in vivo efficacy. We assume this is due to a delayed generation of activated killing in T-cells that is generated in vivo. These experimental results in this model system of human ovarian cancer indicate that transfer of autologous activated cells may have a role in the treatment of ovarian cancer patients.

摘要

在人卵巢癌的体内裸鼠模型中,采用经重组白细胞介素2和γ干扰素体外激活的各种纯化的人淋巴细胞和单核细胞样效应细胞进行过继性细胞治疗。腹腔注射人白细胞介素2激活的大颗粒淋巴细胞群体,在该卵巢癌模型中导致平均存活时间显著延长(30至60天)。此外,以与大颗粒淋巴细胞类似的方式用白细胞介素2激活的T细胞,也显著延长了患有卵巢癌动物的存活时间。相比之下,无论有无γ干扰素激活的单核细胞,均未改善荷瘤小鼠的存活情况。使用直接同位素释放测定法在激活前后测量效应细胞对卵巢癌细胞的功效的体外结果,尤其是活化的自然杀伤细胞,与裸鼠模型中的存活效应相似。然而,T细胞在体外的结果在其体内功效方面有些不一致。我们认为这是由于体内产生的T细胞中活化杀伤的延迟产生。在该人卵巢癌模型系统中的这些实验结果表明,自体活化细胞的转移可能在卵巢癌患者的治疗中发挥作用。

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